Is BEST1 p.Ser231Arg (c.693T>A) pathogenic?

BEST1 p.Ser231Arg (c.693T>A) is classified Likely pathogenic in BEST1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-23). AlphaMissense: likely pathogenic (0.9888); Absent from gnomAD v4.1.

How common is BEST1 p.Ser231Arg (c.693T>A) in the general population?

BEST1 p.Ser231Arg (c.693T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BEST1 p.Ser231Arg (c.693T>A)?

AlphaMissense predicts likely pathogenic (score 0.9888) — an in-silico prediction, not a clinical call.

BEST1 p.Ser231Arg

c.693T>A · rs281865244 · VCV987370

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9888 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9888	likely pathogenic ✓ concordant with ClinVar · top 5% in BEST1
REVEL	0.936	strongly pathogenic-leaning
SaProt	LLR -11.01	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.41	GERP -0.84, phastCons 0.17
Regional constraint	o/e 0.91	unconstrained · MANE · 12 kb · p 0.011 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BEST1
Protein: p.Ser231Arg
Coding: c.693T>A
MANE Select: NM_004183
dbSNP: rs281865244
Type: single nucleotide variant
Location: chr11:61957443 (GRCh38)
Gene constraint: LOEUF 1.28 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.46 · 19 PDB
Residue 231: a UniProt-annotated variant site (in vmd2)

Full BEST1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEST1 p.Ser231Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BEST1 c.1100+1G>C Pathogenic/Likely pathogenic ★★ same type
BEST1 c.1101-1G>C Likely pathogenic ★★ same type
BEST1 c.636+1G>A Pathogenic ★★ same type
BEST1 c.867+97G>A Pathogenic/Likely pathogenic ★★ same type
BEST1 p.Ala10Thr Pathogenic ★★ same type
BEST1 p.Ala10Val Pathogenic ★★ same type
BEST1 p.Ala195Val Pathogenic/Likely pathogenic ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/best1-p-ser231arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown